Whom to Screen for Lipoprotein(a)
Elevated Lipoprotein(a) (Lp(a)) confer at least a 2-fold risk of first and recurrent heart attack, which is almost exactly the order of the risk increment caused by diabetes, smoking or 100 mg/dl increase in LDL-C.1 The European consensus statement 2 recommends that Lp(a) should be measured once in all subjects at intermediate or high risk of CVD (cardiovascular disease) who present with:
- Premature CVD
- Familial hypercholesterolemia
- A family history of premature CVD and/or elevated Lp(a)
- Recurrent CVD events despite statin treatment
- ≥ 3% 10-year risk of fatal CVD according to European guidelines3
- ≥ 10% 10-year risk of fatal and/or nonfatal CAD according to U.S. guidelines4
The CADI Research recommends measuring Lp(a) in the following additional categories of people presenting with:5, 6
- History of recurrent arterial stenosis (narrowing) with or without a stent placement7, 8
- Rapid angiographic progression of CAD
- Children and adults with stroke, venous thromboembolism, deep vein thrombosis, and pulmonary embolism9-12
- Women with endometriosis and various thromboembolic complications of pregnancy such as recurrent miscarriages, still birth, fetal growth retardation, preeclampsia, eclampsia, HELLP syndrome, heart attack or pulmonary embolism (see Lp(a) women)13-23
- All Asian Indians and south Asians between the ages of 2 and 756
When to Screen
Lp(a) level can be measured any time after age 2.6 Repeat measurement is necessary only if treatment for high Lp(a) levels is initiated in order to evaluate therapeutic response.2,5
How to Screen
Measurement of Lp(a) should be made by an assay method that is not affected by the Lp(a) isoform. The International Federation of Clinical Chemists, has developed a reference method, which uses detection antibodies to non-variable kringle 4 type 9 that has been approved by NHLBI and WHO as the standardized assay method.24, 25
Post-hoc analysis of several studies have already demonstrated 50% reduction in CAD risk with aspirin and Lp(a) lowering brought by estrogen.26, 27 Prescription niacin is moderately effective in lowering Lp(a) and a large outcome trial (n=25,000) evaluating the benefit of adding niacin will be completed in 2013. In the mean time those with elevated Lp(a) should be treated to an LDL-C goal of <70 mg/dl.
1. Genser B, Dias KC, Siekmeier R, Stojakovic T, Grammer T, Maerz W. Lipoprotein (a) and risk of cardiovascular disease–a systematic review and meta analysis of prospective studies. Clin Lab. 2011;57(3-4):143-156.
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. Graham I, Atar D, Borch-Johnsen K, Boysen G, Durrington PN. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J. Oct 2007;28(19):2375-2414.
4. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. Jul 13 2004;110(2):227-239.
5. Enas EA. How to Beat the Heart Disease Epidemic among South Asians: A Prevention and Management Guide for Asian Indians and their Doctors. Downers Grove: Advanced Heart Lipid Clinic USA; 2011.
6. 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.
7. Futterman LG, Lemberg L. Lp(a) lipoprotein–an independent risk factor for coronary heart disease after menopause. Am J Crit Care. Jan 2001;10(1):63-67.
8. Desmarais RL, Sarembock IJ, Ayers CR, Vernon SM, Powers ER, Gimple LW. Elevated serum lipoprotein(a) is a risk factor for clinical recurrence after coronary balloon angioplasty. Circulation. Mar 1 1995;91(5):1403-1409.
9. Vormittag R, Vukovich T, Stain M, Lehr S, Minar E, Pabinger I. Lipoprotein (a) in patients with spontaneous venous thromboembolism. Thromb Res. 2007;120(1):15-20.
10. Marcucci R, Liotta AA, Cellai AP, et al. Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism. Am J Med. Dec 1 2003;115(8):601-605.
11. Seki Y, Takahashi H, Shibata A, Aizawa Y. Plasma levels of thrombomodulin and lipoprotein (a) in patients with cerebral thrombosis. Blood Coagul Fibrinolysis. Oct 1997;8(7):391-396.
12. Nagayama M, Shinohara Y, Nagayama T. Lipoprotein(a) and ischemic cerebrovascular disease in young adults. Stroke. Jan 1994;25(1):74-78.
13. Sakai Y, Tomobuchi Y, Toyoda Y, Shinozaki M, Hano T, Nishio I. A premenopausal woman presenting with acute myocardial infarction of three different coronary vessels within 1 year: role of lipoprotein(a). Jpn Circ J. Nov 1998;62(11):849-853.
14. Ogunyemi D, Cuellar F, Ku W, Arkel Y. Association between inherited thrombophilias, antiphospholipid antibodies, and lipoprotein A levels and venous thromboembolism in pregnancy. Am J Perinatol. Jan 2003;20(1):17-24.
15. Berg K, Roald B, Sande H. High Lp(a) lipoprotein level in maternal serum may interfere with placental circulation and cause fetal growth retardation. Clin Genet. 1994;46(1 Spec No):52-56.
16. van Pampus MG, Koopman MM, Wolf H, Buller HR, Prins MH, van den Ende A. Lipoprotein(a) concentrations in women with a history of severe preeclampsia–a case control study. Thromb Haemost. 1999;82(1):10-13.
17. Crook D, Howell R, Sidhu M, Edmonds DK, Stevenson JC. Elevated serum lipoprotein(a) levels in young women with endometriosis. Metabolism. 1997;46(7):735-739.
18. Atsumi T, Khamashta MA, Andujar C, et al. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol. 1998;25(1):69-73.
19. Yamazaki M, Asakura H, Jokaji H, et al. Plasma levels of lipoprotein(a) are elevated in patients with the antiphospholipid antibody syndrome. Thromb Haemost. Apr 1994;71(4):424-427.
20. Szczepanski M, Bauer A, Gardas A, Duchinski T. Antiphospholipid antibodies and lipoprotein (a) in women with recurrent fetal loss. Int J Gynaecol Obstet. Apr 1998;61(1):39-44.
21. Husby H, Roald B, Schjetlein R, Nesheim BI, Berg K. High levels of Lp(a) lipoprotein in a family with cases of severe pre- eclampsia. Clin Genet. 1996;50(1):47-49.
22. Kaminski K, Czuba B, Fiegler P. Predictive usefulness of lipoproteins a -Lp (a) in cases of preeclampsia. Ginekol Pol. 2000;71(8):777-782.
23. Ulm MR, Obwegeser R, Ploeckinger B, Nowotny C, Pidlich J, Sinzinger H. A case of myocardial infarction complicating pregnancy–a role for prostacyclin synthesis stimulating plasma factor and lipoprotein (a)? Thromb Res. 1996;83(3):237-242.
24. Marcovina SM, Albers JJ, Kennedy H, Mei JV, Henderson LO, Hannon WH. International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. IV. Comparability of apolipoprotein B values by use of International Reference Material. Clin Chem. 1994;40(4):586-592.
25. 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.
26. Shlipak MG, Simon JA, Vittinghoff E, et al. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. JAMA. 2000;283(14):1845-1852.
27. Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis. Apr 2009;203(2):371-376.