2.2.3 Lipoprotein (a)
Multiple risk factors usually contribute to the development of atherosclerosis. Hence, family history of premature or aggressive CVD is an important consideration. For example, circulating levels of Lp(a) are inherited and elevated levels have shown to be an independent risk marker for MI. Blood levels of Lp(a) are determined by polymorphism of the LPA gene, coding for the Apo(a) moiety of the Lp(a) particle. It has been shown that Apo(a) size, which depends of the number of kringle IV–type 2 (KIV-2) repeats, inversely correlates with circulating Lp(a) levels.
High levels of Lp(a) have been associated with heart disease since 1970s, but it has been difficult to detect whether Lp(a) actually plays a causative role. Recent findings, however, have provided support for a causal association of Lp(a) with coronary disease. In a publication, Kamstrup and coworkers at the Herlev Hospital, Denmark reported their observed associations of elevated levels of Lp(a) as well as the genetic variation raising the Lp(a) levels with MI risk. These findings were supported by the work of Clarke and colleagues at the University of Oxford, United Kingdom, who identified two LPA variants that were found to be strongly associated with increased Lp(a) levels, a reduced number of KIV-2 repeats, a small Lp(a) size and an increased risk for coronary disease. In an editorial to Kamstrup et al. Thanassoulis and O'Donnell, both affiliated to the National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA, correspond that “this is an important biological finding that elevates the status of Lp(a)”.
The Apo(a) moiety of the Lp(a) particle shares sequence homology with plasminogen, which in circulation is converted to its active form plasmin, an important enzyme that inhibits thrombus formation through fibrinolysis. Recent studies have shown that the plasminogen-like Apo(a) competes with plasminogen for binding to the plasminogen receipt and thus inhibits plasminogen activation and consequently the formation of plasmin. These properties of Apo(a) may explain the association of high Lp(a) concentrations with MI.
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