Lp(a) and Atherothrombosis


  • Extreme elevation of Lipoprotein(a) (Lp(a)) levels predict a 3- to 4-fold increase in risk of heart attack in the general population; the absolute 10-year risks can be as high as 20% in women and 35% in men, even in the absence of elevated LDL-C, non-HDL-C, and other risk factors.1, 2
  • In general, the Lp(a) particle is 10 times more dangerous than LDL-C particles and is associated with accelerated atherosclerosis as well as thrombosis.3  Lp(a) is a genetic variant of LDL (low-density lipoprotein) particle with one molecule of apolipoprotein B100 (apoB) and an additional protein, apo(a), attached via a disulphide bond.4
  • Elevated Lp(a) levels are associated with increased risk of cardiac death, heart attack, stroke, and PAD (peripheral arterial disease), particularly in subjects with small apo(a) (apolipoprotein(a)) isoforms.5-7 Lp(a) level is also a significant predictor of coronary stenosis progression, especially in left main artery as well as central retinal vein occlusion.8, 9
  • Elevated Lp(a) levels can increase the risk of CVD (cardiovascular disease) by multiple mechanisms (see Mechanism of Action).2
  • Although both small isoforms and high Lp(a) level predict CVD risk in dialysis patients, the association with small isoforms is stronger than the association with high Lp(a) concentration.10
  • These recent findings have led the European Atherosclerosis Society to recommend testing of Lp(a) to patients at moderate-to-high risk of CVD and administration of niacin to reduce the levels.2 Although the Europeans consider the cut point for CVD risk from elevated LP(a) at >50 mg/dl or 112 nanomol/L the US cut point is much lower at >30 mg/dl or 75 nanomol.11


1. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population. The Copenhagen City Heart Study. Circulation. Dec 17 2007:176-184.

2. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. Oct 21 2010.

3.  Enas EA, Chacko V, Senthilkumar A, Puthumana N, Mohan V. Elevated lipoprotein(a)–a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis Mon. Jan 2006;52(1):5-50.

4. Utermann G. The mysteries of lipoprotein(a). Science. 1989;246:904-910.

5. Bennet A, Di Angelantonio E, Erqou S, et al. Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease: Large-Scale Prospective Data. Arch Intern Med. Mar 24 2008;168(6):598-608.

6.  Erqou S., Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. Jul 22 2009;302(4):412-423.

7. 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. May 11 2010;55(19):2160-2167.

8. Morita Y, Himeno H, Yakuwa H, Usui T. Serum lipoprotein(a) level and clinical coronary stenosis progression in patients with myocardial infarction: re-revascularization rate is high in patients with high-Lp(a). Circ J. Feb 2006;70(2):156-162.

9. Murata M, Saito T, Takahashi S, Ichinose A. Plasma lipoprotein(a) levels are high in patients with central retinal artery occlusion. Thromb Res. Aug 15 1998;91(4):169-175.

10. Longenecker JC, Klag MJ, Marcovina SM, et al. High lipoprotein(a) levels and small apolipoprotein(a) size prospectively predict cardiovascular events in dialysis patients. J Am Soc Nephrol. Jun 2005;16(6):1794-1802.

11. Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin Chem. Nov 2003;49(11):1785-1796.

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