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Lipoprotein (a) (Lp[a]) consists of an LDL particle that is covalently bound to an additional protein, apolipoprotein (a) (Apo[a]). Apo(a) has high-sequence homology with the coagulation factor plasminogen and, like LDL, Lp(a) contains apolipoprotein B100 (ApoB). Thus, Lp(a) is both proatherogenic and prothrombotic. Lp(a) is an independent risk factor for coronary heart disease (CHD), ischemic stroke, and aortic valve stenosis. Lp(a) has been referred to as "the most atherogenic lipoprotein." The mechanism of increased risk is unclear but most likely involves progression of atherosclerotic stenosis via intimal deposition of cholesterol and promotion of thrombosis via homology to plasminogen.
Concentrations of Lp(a) particles in the blood can be expressed readily by 2 methods: as concentrations of Lp(a) protein or as Lp(a) cholesterol. Mayo’s Cardiovascular Laboratory Medicine measures and reports Lp(a) cholesterol individually (LPAWS / Lipoprotein [a] Cholesterol, Serum) and as a part of the lipoprotein profile (LMPP / Lipoprotein Metabolism Profile). The cholesterol content of Lp(a) particles varies little, and Lp(a) can contain significant proportions of the serum cholesterol.
Unlike Lp(a) cholesterol, accurate immunochemical measurement of Lp(a)-specific protein, is complicated by the heterogeneity of Lp(a) molecular size. Due to the large number of polymorphisms in the population any given individual can have an Apo(a) protein between 240 to 800 kDa. This heterogeneity leads to inaccuracies when results are expressed in terms of mg/dL of protein. In addition, the degree of atherogenicity of the Lp(a) particle may depend on the molecular size of the Lp(a)-specific protein.
Serum concentrations of Lp(a) are related to genetic factors, and are largely unaffected by diet, exercise and lipid-lowering pharmaceuticals. However, in a patient with additional modifiable CHD risk factors, more aggressive therapy to normalize these factors may be indicated if the Lp(a) value is also increased.
Cardiovascular disease (CVD) risk refinement in patients with moderate or high risk based on conventional risk factors
The frequency distribution of serum lipoprotein (a) (Lp[a]) concentrations is markedly skewed toward the low end, with approximately 85% of the population having concentrations <30 mg/dL.
Lp(a) concentrations >30 mg/dL are associated with 2- to 3-fold increased risk of cardiovascular events independent of conventional risk markers.
Epidemiologic studies have shown Lp(a) concentrations are lowest in non-Hispanic Caucasians, Chinese, and Japanese. Hispanics have slightly higher median Lp(a) concentrations and in African Americans, the median Lp(a) serum concentration is approximately 2 times higher than in Caucasians. In most cases, the preferred test for quantifying Lp(a) is LPAWS / Lipoprotein (a) Cholesterol, Serum.
Not recommended as a screening test in the healthy population.
< or =30 mg/dL
Values >30 mg/dL may suggest increased risk of coronary heart disease.
1. Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, et al: Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009 Jul 22;302(4):412-423
2. Lackner C, Cohen JC, Hobbs HH: Molecular definition of the extreme size polymorphism in apolipoprotein(a). Hum Mol Genet 1993;2:933-940
3. Albers JJ, Slee A, O'Brien KD, et al: Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol 2013 Oct 22;62(17):1575-1579
4. Erqou S, Thompson A, Di Angelantonio E, et al: Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol 2010 May 11;55(19):2160-2167