Lp (a) and Severity of Heart Disease

 Severity of Atherosclerosis and Lp (a) 

  • Transgenic animals expressing human apolipoprotein(a) develop spontaneous atherosclerosis (plaque build-up) more frequently while on a low-fat diet, compared to non-transgenic animals.1 Strikingly, transgenic animals develop more extensive atherosclerotic lesions when given a cholesterol-rich diet compared to non-transgenic animals given the same diet.2 Similar phenomena occur in humans.3
  • Lipoprotein(a) (Lp(a)) is not found in normal arterial wall but accumulates in atherosclerotic plaques  to an extent proportional to blood levels. Lp(a) is taken up in plaque more avidly than LDL-C, with the ratio of Lp(a) to LDL-C in plaque being about three times higher than in blood.3
  • Elevated Lp(a) levels are related to early atherosclerosis as measured by brachial and coronary artery reactivity, carotid intimal medial thickness, coronary artery calcification, and transesophageal echocardiography.4-7
  • Unlike other traditional CAD (coronary artery disease) risk factors (such as high blood pressure, smoking, and high cholesterol), elevated Lp(a) levels are highly correlated with rapid progression and severity of CAD as evaluated by coronary angiogram and/or autopsy studies.6-16
  • Lp(a) levels were significantly correlated with the number of critically narrowed coronary arteries, the severity of narrowing, and the proportional length of diseased artery on angiogram; no other lipoprotein variable was significantly correlated with all three of these features.17
  • Patients with CAD and high Lp(a) have poor survival even when treated with statin medications, and this underscores the need for more aggressive treatment including the use of prescription niacin.18-20
  • A low level of HDL-C, a high level of Lp(a), and diabetes are significant predictors of severe or high-risk CAD (defined as triple-vessel disease or ejection fraction <50%). This combination is rare in Japanese, Chinese, and blacks, but exceedingly common among Indians and probably accounts for the malignant heart disease among young Indians.21


1. Sun H, Unoki H, Wang X, et al. Lipoprotein(a) enhances advanced atherosclerosis and vascular calcification in WHHL transgenic rabbits expressing human apolipoprotein(a). J Biol Chem. Dec 6 2002;277(49):47486-47492.

2. Fan J, Shimoyamada H, Sun H, Marcovina S, Honda K, Watanabe T. Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet. Arteriosclerosis, thrombosis, and vascular biology. Jan 2001;21(1):88-94.

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. Peltier M, Iannetta Peltier MC, Sarano ME, Lesbre JP, Colas JL, Tribouilloy CM. Elevated serum lipoprotein(a) level is an independent marker of severity of thoracic aortic atherosclerosis. Chest. May 2002;121(5):1589-1594.

5. Ryu SK, Hong BK, Kwon HM, et al. Age-related contribution of Lp(a) with coronary artery calcification in patients with acute coronary syndrome: a potential role of metabolic disorder in calcified plaque. Yonsei Med J. Jun 30 2003;44(3):445-453.

6. Terres W, Tatsis E, Pfalzer B, Beil FU, Beisiegel U, Hamm CW. Rapid angiographic progression of coronary artery disease in patients with elevated lipoprotein(a). Circulation. 1995;91(4):948-950.

7. Dangas G, Ambrose JA, D’Agate DJ, et al. Correlation of serum lipoprotein(a) with the angiographic and clinical presentation of coronary artery disease. Am J Cardiol. Feb 15 1999;83(4):583-585, A587.

8. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study. Clinical cardiology. Mar 1995;18(3):131-135.

9. Matsumoto Y, Daida H, Watanabe Y, et al. High level of lipoprotein(a) is a strong predictor for progression of coronary artery disease. J Atheroscler Thromb. 1998;5(2):47-53.

10. Tamura A, Watanabe T, Mikuriya Y, Nasu M. Serum lipoprotein(a) concentrations are related to coronary disease progression without new myocardial infarction. Br Heart J. Oct 1995;74(4):365-369.

11. Zampoulakis JD, Kyriakousi AA, Poralis KA, et al. Lipoprotein(a) is related to the extent of lesions in the coronary vasculature and to unstable coronary syndromes. Clinical cardiology. 2000;23(12):895-900.

12. Wang XL, Tam C, Mc Credie R, Wilken D. Determinants of severity of coronary artery disease in Australian men and women. Circulation. 1994;89:1974 – 1981.

13. Wang XL, Cranney G, Wilcken DE. Lp(a) and conventional risk profiles predict the severity of coronary stenosis in high-risk hospital-based patients. Aust N Z J Med. 2000;30(3):333-338.

14. Gazzaruso C, Geroldi D, Garzaniti A, et al. Apolipoprotein(a) phenotypes as genetic markers of coronary atherosclerosis severity. Int J Cardiol. 1998;64(3):277-284.

15. Sawabe M., Tanaka N, Nakahara K, et al. High lipoprotein(a) level promotes both coronary atherosclerosis and myocardial infarction: a path analysis using a large number of autopsy cases. Heart (British Cardiac Society). Dec 2009;95(24):1997-2002.

16. Bolibar I., Thompson SG, von Eckardstein A, Sandkamp M, Assmann G. Dose-response relationships of serum lipid measurements with the extent of coronary stenosis. Strong, independent, and comprehensive. ECAT Angina Pectoris Study Group. Arteriosclerosis, thrombosis, and vascular biology. Aug 1995;15(8):1035-1042.

17. Budde T, Fechtrup C, Bosenberg E, et al. Plasma Lp(a) levels correlate with number, severity, and length- extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis. Arterioscler Thromb. 1994;14(11):1730-1736.

18. Glader CA, Birgander LS, Stenlund H, Dahlen GH. Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden. Journal of internal medicine. Jul 2002;252(1):27-35.

19. Berg K, Dahlen G, Christophersen B, Cook T, Kjekshus J, Pedersen T. Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study. Clinical genetics. 1997;52(5):254-261.

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

21. Miwa K, Nakagawa K. Risk factors that discriminate ‘high- risk’ from ‘low-risk’ Japanese patients with coronary artery disease. Jpn Circ J. Nov 2000;64(11):825-830.

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