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on September 2, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print September 2, 2004, doi: 10.1161/01.ATV.0000144010.55563.63
A more recent version of this article appeared on December 1, 2004
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*Substance via MeSH

Submitted on July 14, 2004
Accepted on August 23, 2004

Lipoprotein(a): An Elusive Cardiovascular Risk Factor

Lars Berglund * and Rajasekhar Ramakrishnan

From Department of Medicine (L.B.), University of California, Davis and the VA Northern California Health Care System (L.B.); Department of Pediatrics (R.R.), Columbia University, New York, NY.

* To whom correspondence should be addressed. E-mail: lberglund{at}ucdavis.edu.

Abstract--Lipoprotein (a) [Lp(a)], is present only in humans, Old World nonhuman primates, and the European hedgehog. Lp(a) has many properties in common with low-density lipoprotein (LDL) but contains a unique protein, apo(a), which is structurally different from other apolipoproteins. The size of the apo(a) gene is highly variable, resulting in the protein molecular weight ranging from 300 to 800 kDa; this large variation may be caused by neutral evolution in the absence of any selection advantage. Apo(a) influences to a major extent metabolic and physicochemical properties of Lp(a), and the size polymorphism of the apo(a) gene contributes to the pronounced heterogeneity of Lp(a). There is an inverse relationship between apo(a) size and Lp(a) levels; however, this pattern is complex. For a given apo(a) size, there is a considerable variation in Lp(a) levels across individuals, underscoring the importance to assess allele-specific Lp(a) levels. Further, Lp(a) levels differ between populations, and Africans (or blacks) have generally higher levels than Asians and whites, adjusting for apo(a) sizes. In addition to the apo(a) size polymorphism, an upstream pentanucleotide repeat (TTTTAn) affects Lp(a) levels. Several meta-analyses have provided support for an association between Lp(a) and coronary artery disease, and the levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with cardiovascular disease or with preclinical vascular changes. Further, there is an interaction between Lp(a) and other risk factors for cardiovascular disease. The physiological role of Lp(a) is unknown, although a majority of studies implicate Lp(a) as a risk factor.




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